Similar Items

Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds

Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds

A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c–3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P...

Full description

Saved in:
Bibliographic Details
Main Authors: Tukulula, Matshawandile, Njoroge, Mathew, Abay, Efrem T., Mugumbate, Grace C., Wiesner, Lubbe, Taylor, Dale, Gibhard, Liezl, Norman, Jennifer, Swart, Kenneth J., Gut, Jiri, Rosenthal, Philip J., Barteau, Samuel, Streckfuss, Judith, Kameni-Tcheudji, Jacques, Chibale, Kelly
Format: Article
Language:English
Published: American Chemical Society 2022
Subjects:
Aminoquinolines
antiplasmodial activity
pharmacokinetics
Plasma protein binding
Online Access:https://doi.org/10.1021/ml400311r
http://hdl.handle.net/11408/4922
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c–3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4–6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7.